Spontaneously hyperlipidemic (SHL) mice are Japanese wild
mice (Mus musculus molossinus KOR) with gross disruption of the gene
for apolipoprotein E. These SHL mice (hereafter KOR-Apoeshl)
are superhypercholesterolemic and develop severe xanthoma, but their atherosclerosis
is relatively mild compared with Apoe knock out mice. First, we tested
whether this distinction between KOR-Apoeshl and Apoe
knockout mice is due to additional mutation of the Apoc1 and/or Apoc2
genes, which localize adjacent to the Apoe gene, in KOR-Apoeshl.
Southern blot analysis, however, found no gross disruption of these two genes.
Next, we tested whether the phenotypic distinction is due to differences in
the genetic background in two strains of apolipoprotein E deficient mice. To
this end, we established three lines of congenic SHL mice with a genetic background
of C57BL/6, BALB/c or C3H/He mice, and named them, respectively, C57BL/6. KOR-
Apoeshl (hereafter B6. KOR- Apoeshl), BALB/c.
KOR-Apoesh (C.KOR-Apoeshl ) and C3H/He.KOR-Apoesh
(C3.KOR-Apoeshl). Hypercholesterolemia was most severe in
KOR-Apoeshl followed by others in a following manner; KOR-
Apoeshl >> C3.KOR-Apoeshl > C.KOR-Apoeshl
> B6.KOR-Apoeshl In contrast, atherosclerosis was most
severe in B6.KOR-Apoeshl followed by the others in this
manner: B6.KOR-Apoeshl > C.KOR-Apoeshl
>> C3.KOR-Apoeshl KOR-Apoeshl.
This order, however, did not match that in xanthoma, which was highly prominent
in KOR-Apoeshl but mild in B6.KOR-Apoeshl,
C.KOR-Apoeshl and C3.KOR-Apoeshl. These
clear distinctions suggest that the severity of each of the phenotypes, i.e.,
hypercholesterolemia, atherosclerosis and xanthoma, is determined by distinct
genetic backgrounds independently. Japanese wild mice possibly have suppressor
genes for atherosclerosis, while laboratory mice have suppressor genes for xanthoma/hyperlipidemia.
Or enhancer genes for each phenotype may exist. Prominent distinctions of the
phenotypes between SHL mice with the genetic background of wild mice, and those
with that of laboratory mice background are useful for identification of the
genes responsible for atherosclerosis, hypercholesterolemia and xanthoma that
are due to apolipoprotein E deficiency.